Moe version 2008

Molecular Operating Environment (MOE version 2008.10) by Chemical Computing Group (CCG) was used for the docking studies (Inc. CCG, 2016 ). The protein preparation steps involved 3D protonation, energy minimization, and active site identification. The X-ray crystallographic structure of CDK8/CycC enzyme co-crystallized with Senexin A (PDB code 4f7s) was obtained from the Protein Data Bank (Schneider et al., 2013 (link)). The enzyme was prepared for virtual docking studies where: (i) the ligand molecule with any existing solvent molecules were removed. (ii) Hydrogen atoms were added to the structure with their standard geometry. To visualize the binding pocket, alpha spheres were created followed by the generation of dummy atoms on the centers of these spheres. The pocket was found to be a deep cavity lined with the amino acid residues including both hydrophobic and hydrophilic amino acids. Energy minimization tool MOPAC 7.0 was applied for the tilted compounds. (iii) MOE Alpha Site Finder was used for the active sites search and dummy atoms were created from the obtained alpha spheres. The obtained ligand-enzyme complex model was then used in calculating the energy parameters using MMFF94x force field energy calculation and predicting the ligand-enzyme interactions.

Docking studies for the synthesized products were performed using Molecular Operating Environment (MOE) version 2008.10 (Chemical Computing Group Inc., Montreal, QC, Canada). Compounds 5a–e were built using the builder interface of the MOE program and subjected to energy minimization using the included Forcefield MMFF94x calculations. The X-crystallographic structure of E. coli Enoyl reductase (PDB ID: 1LXC) which is complexed with ((E)-3-(6-aminopyridin-3-yl)-N-methyl-N-((1-methyl-1H-indol-2-yl)methyl) acrylamide (PDB ID: AYM)) (NAD), that was obtained from Protein Data Bank.